What is the recommended treatment for persistent hepatitis C infection?

Treatment for Persistent Hepatitis C Infection

The recommended first-line treatment for persistent hepatitis C infection is a 12-week course of the fixed-dose combination of sofosbuvir and velpatasvir (400mg/100mg) taken once daily, regardless of HCV genotype (1-6), prior treatment experience, or cirrhosis status (except decompensated cirrhosis, which requires addition of ribavirin). 1, 2

Treatment Regimen Selection Based on Patient Characteristics

Standard Treatment Approach

• For most patients (treatment-naïve or experienced, with or without compensated cirrhosis):
  • Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks 1, 3
  • This pangenotypic regimen is effective across all HCV genotypes (1-6)
  • SVR12 rates consistently exceed 95% in most patient populations 4

Special Populations

Patients with Decompensated Cirrhosis (Child-Pugh B or C):

• Sofosbuvir/velpatasvir 400mg/100mg once daily PLUS weight-based ribavirin for 12 weeks 1, 3
  • Ribavirin dosing: 1,000 mg daily for patients <75 kg and 1,200 mg daily for patients ≥75 kg, divided twice daily 3
  • Important: Protease inhibitors (including glecaprevir/pibrentasvir) are contraindicated in decompensated cirrhosis due to risk of toxicity 1

Genotype 3 Patients with Compensated Cirrhosis:

• Treatment-naïve: Three options based on resistance testing 1:

  1. Sofosbuvir/velpatasvir + ribavirin for 12 weeks
  2. Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks
  3. Glecaprevir/pibrentasvir for 12 weeks (can consider 8 weeks, but more data needed)

• Treatment-experienced: Three options 1:

  1. Sofosbuvir/velpatasvir + ribavirin for 12 weeks
  2. Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks
  3. Glecaprevir/pibrentasvir for 16 weeks

• Note: If NS5A Y93H resistance testing is available, only patients with this mutation require ribavirin addition or triple therapy 1

Monitoring During and After Treatment

1. Pre-treatment testing:

   • Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before starting treatment 3
   • Assess for potential drug interactions, especially with amiodarone (contraindicated), proton pump inhibitors, and antiretrovirals 2

2. During treatment:

   • No routine HCV RNA monitoring required during treatment 2
   • Monitor for adverse effects (headache, fatigue, nausea most common) 2, 5
   • For patients with cirrhosis: closer monitoring for signs of decompensation 2
   • For HBV/HCV co-infected patients: monitor for HBV reactivation 3

3. Post-treatment:

   • HCV RNA testing at 12 weeks post-treatment to confirm SVR12 1, 2
   • For high-risk patients or those at risk of reinfection, consider SVR24 testing 1

Important Considerations and Potential Pitfalls

1. HBV reactivation risk:

   • HBV reactivation has been reported in HCV/HBV co-infected patients during or after DAA therapy
   • Some cases have resulted in fulminant hepatitis, hepatic failure, and death
   • Monitor co-infected patients and initiate appropriate HBV management if indicated 3

2. Drug interactions:

   • Avoid co-administration with amiodarone due to risk of serious bradycardia 2
   • Check for interactions with commonly used medications (statins, antihypertensives, antiretrovirals) 2

3. Genotype 3b with cirrhosis:

   • Lower efficacy observed (50% SVR12) in patients with HCV genotype 3b and cirrhosis 6
   • Consider resistance testing and alternative regimens for these patients

4. Treatment adherence:

   • Single tablet regimen improves adherence 2
   • Emphasize importance of completing full course of treatment

The sofosbuvir/velpatasvir regimen offers a simple, highly effective pangenotypic treatment option with minimal monitoring requirements and excellent tolerability, making it ideal for most patients with persistent HCV infection 7, 4.